Triphenylphosphine → N-Trifluoroacetyl-8-chloro-1-methylene-2,3,4,5-tetrahydro-1H-3-benzazepine
Reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1I)=[O:4].CC([O-])=O.[K+].[CH:23]1[CH:28]=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=C[CH:24]=1>CN(C)C=O.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]([F:17])([F:16])[C:3]([N:5]1[CH2:28][C:23](=[CH2:24])[C:9]2[CH:10]=[C:11]([Cl:14])[CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6]1)=[O:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 105 °C
Procedure
A solution of N-allyl, N-trifluoroacetyl-2-iodo-4-chlorophenethylamine (0.76 g, 1.8 mmol) in dimethylformamide (20 mL) was treated with KOAc (0.53 g, 5.4 mmol), n-Bu4NBr (0.58 g, 1.8 mmol), PPh3 (0.047 g, 0.18 mmol), Pd(OAc)2 (0.041 g, 0.18 mmol) and stirred overnight at 105° C. The product mixture was cooled to 20° C., filtered, diluted with water (100 mL), extracted with ether (3×100 mL), the combined organic phases washed with water (100 mL), brine (100 mL), dried with Na2SO4 and concentrated. Flash chromatography (10% EtOAc in hexane, silica) resulted in 0.228 g of a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.29 (s, 1H), 7.18 (m, 1H), 7.04 (m, 1H), 5.38 (m, 2H), 5.40 (d, J=16 Hz, 2H), 3.80 (m, 2H), 3.00 (m, 2H). MS calculated for C13H11ClF3NO+H: 290, observed: 290.
Workup
- temperatureThe product mixture was cooled to 20° C.
- filtrationfiltered
- additiondiluted with water (100 mL)
- extractionextracted with ether (3×100 mL)
- washthe combined organic phases washed with water (100 mL), brine (100 mL)
- dry with materialdried with Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-371c3530a0184899a2ceeae3f932545b
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546378B2
Reaction notes
Loading…